title: Human umbilical cord mesenchymal stem cells ameliorate mice trinitrobenzene sulfonic acid (TNBS)-induced colitis.
abstract: Mesenchymal stem cells (MSCs), which are poorly immunogenic and have potent immunosuppressive activities, have emerged as a promising candidate for cellular therapeutics for the treatment of disorders caused by abnormal immune responses. In this study we investigated whether human umbilical  cord-derived mesenchymal stem cells (hUC-MSCs) could ameliorate colitis in a trinitrobenzene sulfonic acid (TNBS)-induced colitis model. TNBS-treated colitic mice were infused with hUC-MSCs or vehicle control. The mice were sacrificed on day 1, 3, and 5 after infusion, and their clinical and  pathological conditions were evaluated by body weight, colon length, and histological analysis. The expression levels of proinflammatory cytokine proteins in colon were examined by ELISA. The homing of hUC-MSCs was studied by live in vivo imaging and immunofluorescent microscopy. hUC-MSCs  were found to migrate to the inflamed colon and effectively treated the colitic mice with improved clinical and pathological signs. The levels of IL-17 and IL-23 as well as IFN-γ and IL-6 were significantly lower in the colon tissues of the hUC-MSC-treated mice in comparison with the  vehicle-treated mice. Coculture experiments showed that hUC-MSCs not only could inhibit IFN-γ expression but also significantly inhibit IL-17 production by lamina propria mononuclear cells (LPMCs) or splenocytes of the colitic mice or by those isolated from normal animals and stimulated  with IL-23. Systemically infused hUC-MSCs could home to the inflamed colon and effectively ameliorate colitis. In addition to the known suppressive effects on Th1-type immune responses, hUC-MSC-mediated modulation of IL-23/IL-17 regulated inflammatory reactions also plays an important role  in the amelioration of colitis.
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, PR China.
authors.forename: Lu
authors.initials: L
authors.lastname: Liang
authors.forename: Chunlan
authors.initials: C
authors.lastname: Dong
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Chen
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Fang
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.forename: Meng
authors.initials: M
authors.lastname: Liu
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Zhang
authors.forename: Dong Sheng
authors.initials: DS
authors.lastname: Gu
authors.forename: Ding
authors.initials: D
authors.lastname: Wang
authors.forename: Weiting
authors.initials: W
authors.lastname: Du
authors.forename: Delin
authors.initials: D
authors.lastname: Zhu
authors.forename: Zhong Chao
authors.initials: ZC
authors.lastname: Han
mesh_terms: D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D002469:Cell Separation; D002470:Cell Survival; D018920:Coculture Techniques; D003092:Colitis / Q000473:pathology* / Q000628:therapy*; D003106:Colon / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D009092:Mucous Membrane / Q000473:pathology; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D014302:Trinitrobenzenesulfonic Acid; D014470:Umbilical Cord / Q000166:cytology*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D014302:Trinitrobenzenesulfonic Acid